Ann Thorac Surg 1995;60:964-969
© 1995 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Treatment of Multiple Primary Squamous Cell Carcinomas of the Lung
Shinya Murakami, MD,
Yoh Watanabe, MD,
Hiroshi Saitoh, MD,
Ryohei Yamashita, MD,
Junzo Shimizu, MD,
Makoto Oda, MD,
Yoshinobu Hayashi, MD
Department of Surgery, Kanazawa University School of Medicine, Kanazawa, and Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
Accepted for publication May 19, 1995.
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Abstract
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Background. The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy.
Materials. We treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3% of all squamous cell carcinoma patients undergoing resection.
Results. Two patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation.
Conclusions. The surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.
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Introduction
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The prevalence of multiple primary bronchogenic carcinomas has been increasing as a result of improvements in early detection and cancer therapy [1, 2]. Especially in Japan, multiple squamous cell carcinoma (SCC) of the tracheobronchial tree and lung has been reported with increasing frequency, partly as a result of the use of sputum cytology in mass screening and in lung cancer patients undergoing resection, and recently multicentric carcinogenesis was reported to be one of the major problems that affected prognosis [3–5].
Although pulmonary resection remains the most effective treatment for patients with non-small cell lung cancer, most patients with SCC are smokers and have poor pulmonary reserve. Moreover, there are anatomic restrictions on reoperation for multiple SCC, because SCC is likely to occur at the hilar region of the lung. Recently, endobronchial treatments for lung cancer (laser ablation, photodynamic therapy [6], and endobronchial brachytherapy) have been developed, but complete remission may be obtained only in patients with carcinoma in situ or microinvasive SCC. We have adopted an aggressive policy regarding further surgical intervention in patients with recurrent and second primary lung cancer [7]. In this article, the results of treatment of multiple SCC of the tracheobronchial tree and lung are reported, and the operative methods are discussed.
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Material and Methods
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We used the following criteria modified from Martini and Melamed [8] to identify patients with multiple SCC (same histology): (1) origin from carcinoma in situ, and (2) the secondary cancer was located in a different lobe or lung, without any carcinoma in the lymphatic system common to both or extrapulmonary metastases at the time of diagnosis.
In defining early hilar cancer, the criteria proposed by the Japan Lung Cancer Society were used. The Japan Lung Cancer Society defines early hilar lung cancers as tumors fulfilling the following three histologic criteria: (1) the lesion is localized proximal to the segmental bronchi; (2) the depth of tumor invasion is confined to the bronchial wall; and (3) there are no lymph node metastases or distant metastases. The bronchoscopic findings for the lesion were classified as superficial type, nodular type, and polypoid type, also using the Japan Lung Cancer Society classification of the bronchoscopic finding (Fig 1
). Microscopic examination of serial sections of the resected specimens was performed to determine the final diagnosis of early hilar lung cancer as well as the extent of each lesion.
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Fig 1. . Bronchoscopic views of the three types of early hilar cancer defined by the Japan Lung Cancer Society (JLCS). (Left) superficial type; (middle) nodular type; (right) polypoid type. The JLCS defines early hilar lung cancers as tumors fulfilling the following criteria: the lesion is localized proximal to the segmental bronchi; the depth of tumor invasion is confined to the bronchial wall; and there are no lymph node metastases or distant metastases. (A = epithelial layer; B = subepithelial layer; C = muscular layer; D = cartilage.)
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Between 1961 and 1994, we treated 14 patients with multiple SCC of the tracheobronchial tree and lung, which corresponded to 2.3% of all SCC patients undergoing resection. All patients were men and heavy smokers, their smoking index (an average number of cigarettes per day times years smoked) ranged from 800 to 1,600. Six patients had synchronous lesions, and eight metachronous lesions (1 patient had three lesions). The average interval between the first resection and the second treatment for metachronous SCC was 47 months (range, 24 to 76 months). Three second primary tumors were located in the ipsilateral lung and 10 in the contralateral lung.
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Results
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Synchronous Multiple Squamous Cell Carcinomas
The lesions in all 6 patients with synchronous lesions were located in the bilateral lungs (Table 1). The secondary lesions in 3 patients (patients 1, 2, and 3) were superficial and minute (less than 5 mm). Their advanced tumors were resected and the minute contralateral lesions were treated with neodymium-yttrium aluminum garnet laser ablation. Patient 4 had a peripheral T2 tumor in the left upper division and a hilar T1 tumor, computed tomographic scan revealed tumor invasion extending beyond the bronchial wall. He underwent left upper division segmentectomy, but the tumor of the right bronchus was treated with irradiation and neodymium-yttrium aluminum garnet laser ablation because of his poor pulmonary reserve. The irradiation was very effective, and the right bronchial tumor was thought to have resolved. Tumor recurrence was noted 1 year later, and he is presently alive with cancer.
In the other 2 patients with synchronous SCC, the secondary tumors were hilar lesions classified as nodular or polypoid type with extensive spread and it was difficult to determine the extent of the lesions. The polypoid tumor in patient 5 occluded the B6, and the nodular tumor recurred after chemotherapy in patient 6 (Fig 2A). These patients underwent sleeve segmentectomy 1 and 4 months after the first operation, respectively, with good results (Fig 2B). They have been alive without recurrence for 24 and 6 months after the second operation, respectively.
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Fig 2. . (A) Bronchoscopic appearance of the right intermediate bronchus in patient 6. An endobronchial nodular tumor is seen at the spur of B6 and basal bronchus. (B) Postoperative bronchoscopic finding in patient 6. A small cicatrication is seen, but the orifices of the segmental bronchus are patent.
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Metachronous Multiple Squamous Cell Carcinomas
Eight patients had metachronous lesions, consisting of three lesions in the ipsilateral lung, four in the contralateral lung, and two in the trachea. Two small peripheral T1 tumors (in patients 8 and 9) were detected on the chest roentgenogram during follow-up after the first operation. These patients underwent partial resection or segmentectomy (Table 2).
Six patients had hilar type second primary tumors, and 1 had a third lesion. Three hilar tumors were also found on chest roentgenogram. Two patients had good pulmonary reserve. Patient 10, in whom the secondary tumor obstructed the left lower bronchus, underwent sleeve lobectomy. He has survived for 10 years after the second operation without a recurrence. Patient 11 had advanced second primary cancer (T2 N2 M0) and underwent lobectomy, but he died of recurrence 14 months after the second operation. The tumor in patient 7 stenosed the left main bronchus. He had suffered from obstructive pneumonia several times. He was treated by conservative methods because of his advanced age (81 years old), but he died of bleeding during the neodymium-yttrium aluminum garnet laser ablation. In three patients (patients 12, 13, and 14), a total of four roentgenographically occult bronchogenic SCC were detected with sputum cytology during follow-up after the first operation. Three lesions were treated with parenchymal-sparing sleeve resection consisting of sleeve segmentectomy, sleeve bronchial resection, and sleeve tracheal resection in one lesion each. Two of these tumors were hilar early cancer with subepithelial invasion, and the other showed minute invasion outside the bronchial wall detected by microscopic examination of serial sections. The patient with the third primary cancer was treated with neodymium-yttrium aluminum garnet ablation. Two patients tolerated the second operation well, but patient 13, who underwent sleeve tracheal resection, died of cerebral infarction 3 months after the second operation.
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Comment
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The occurrence of more than one carcinoma in an organ is almost always the consequence of the effect of carcinogens causing tumor progression in the epithelium through the stages of dysplasia, carcinoma in situ, and invasive malignancy. In the patient with lung cancer, occurrence of a second primary malignant lung neoplasm has been described in more than 10% of the patients surviving for 3 or more years [1], and the frequency of multiple SCC in particular has been reported to be very high [2]. The detection rate of multicentricity in occult bronchogenic SCC was reported to be 32% by Martini and Melamed [9] and 27.4% (7% synchronous and 20.4% metachronous) by Cortese and colleagues [10]. Saito and co-workers [5] reported 12 patients with synchronous multiple SCC and 13 patients with metachronous SCC among 127 patients with resected roentgenographically occult bronchogenic SCC. At our institution, the detection rate of second primary SCC of the tracheobronchial tree was 2.3% among all patients with SCC and 10.5% (4 of 38 patients) among those with first hilar early SCC as defined by the Japan Lung Cancer Society. As the incidence of second primary cancer appears to be high in roentgenographically occult bronchogenic SCC and hilar SCC, we routinely perform repeated sputum cytology studies and bronchoscopic examinations every 6 months.
There are several studies in the literature describing the treatment strategy options in patients with multiple primary lung tumors. Most thoracic surgeons would probably agree that a second pulmonary tumor should be resected if the lung lesion is solitary, if there is no evidence of distant metastases, and if the patient has adequate pulmonary reserve. Jensik [11] and Mathisen [12] and their colleagues reported that second and third surgical efforts for recurring bronchogenic cancer are justified and significantly prolong survival, and that the use of segmental or subsegmental resective techniques provides superior survival results. Deschamps and colleagues [13] also reported that pulmonary resection with as much conservation as possible is safe and offers the greatest possibility of long-term patient survival when a second primary lung cancer is detected. We consider segmentectomy or partial resection to be sufficient for the treatment of patients with peripheral secondary lung cancer without lymph node metastases at the time of operation.
This principle of treatment for second primary lung cancer, of conserving the residual lung function to the greatest extent possible, is also applied in centrally located lung cancers, especially in hilar early SCC. Several nonsurgical endoscopic modalities (neodymium-yttrium aluminum garnet laser ablation, photodynamic therapy, and brachytherapy) are currently used for the treatment of hilar lung cancer. Endobronchial photodynamic therapy was first investigated by a group at Tokyo Medical College [6] and a group at the Mayo Clinic. Cortese and Kinsey [14] reported that photodynamic therapy was apparently effective for tumor invasion limited to a depth of up to 0.5 cm from the bronchial surface with neither penetration through the bronchial wall nor lymph node metastasis. Okunaka and colleagues [15] described the indications for photodynamic therapy in multiple primary lung cancers as follows: exclusively bronchoscopically accessible superficial (Tis N0 M0) lesions, stage I lesions in patients with poor pulmonary function or those who refuse operation, stage I lesions subject to palliative treatment in curative resection patients, and advanced lesions requiring palliation. In 1993, Furuse and colleagues [16], in a report of the results of a prospective phase II study by the Japan Lung Cancer Photodynamic Therapy Study Group, described that photodynamic therapy had excellent effectiveness in the treatment of tumors with limited longitudinal extent (less than 1 cm) in centrally located early-stage lung cancer and when the tumor had a visible distal margin. They emphasized that there was a 10% local recurrence rate and that local recurrence was likely to occur when the distal tumor margin had not been clearly visible endoscopically and, as a result, these lesions had not been completely irradiated. Saito and co-workers [5] reported that limited resection was still the most reliable treatment for metachronous multiple primary lung cancer other than in situ or microinvasive SCC located at the hilus or trachea. We performed neodymium-yttrium aluminum garnet laser ablation in three of our patients with small synchronous primary hilar SCC, which were bronchoscopically superficial and less than 5 mm in diameter, and in 1 patient with small polypoid tumor of the trachea (the third primary tumor). In these lesions, the distal tumor margin was clearly visible endoscopically. The patients were all alive 20 to 84 months after the laser treatment.
Brachytherapy has been used for unresectable or residual lung cancer using permanently implantable sources at the first treatment. Recent developments in this field include the use of flexible bronchoscopy and the placement of a flexible sheath that is subsequently loaded with radiation sources [17, 18]. Reports regarding the use of this technique for the early hilar cancer remain sporadic and anecdotal. Only a few hospitals in Japan have the necessary equipment, and we have not yet performed brachytherapy.
Patients with early hilar cancer as defined by the Japan Lung Cancer Society or minute invasive cancer outside the bronchial wall are the most appropriate candidates for bronchoplastic operation because they have the potential for long-term disease-free survival. In our experience with 38 patients who had exclusively first early lung cancers, the 5-year survival rate (Kaplan-Meier) was 100%, and the cause of death was most commonly second primary lung cancer, malignant tumors of other organs, or other diseases. Because of the multiplicity of early hilar SCC and its good prognosis, it has been our policy to attempt limited operations to preserve to the greatest extent possible the functioning of the lung tissue, if the lesion is of limited extent and can be completely removed by such a procedure. In 1991, we reported the functional advantage of parenchymal-sparing operation for early hilar lung cancer [19]. Parenchymal-sparing operation had a favorable effect on pulmonary function, as verified by both conventional pulmonary function tests, and perfusion and ventilation scan. This policy also applies in second primary SCC, if the lesion is thought to be in the early stage based on the bronchoscopic findings. Five patients underwent parenchymal-sparing bronchoplasty, because the second primary tumors were of the nodular or polypoid type, and the distal tumor margins were not clearly visible endoscopically. Four tumors invaded the subepithelial layer and one had minute invasion outside the bronchial wall. Figure 3 shows the operative methods that were performed in this group. The S6 sleeve segmentectomy was the most practical method, but other methods that we think may be useful include sleeve middle lobe lobectomy, carinal or second carinal resection, and sleeve upper division or lingular segmentectomy.
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Fig 3. . Operative schema of the parenchymal-sparing tracheobronchoplasty for second primary squamous cell carcinoma in 5 patients. The S6 sleeve segmentectomy is the most practical method.
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In conclusion, our therapeutic policies for second or third SCC of the tracheobronchial tree are as follows: (1) In a patient with peripheral tumor without lymph node metastases, segmentectomy or partial resection of the lung would be sufficient procedure. (2) In a patient with roentgenographically occult SCC with superficial spread of less than 1 cm, we perform bronchoscopic laser therapy. (3) For an endobronchial tumor that is of the nodular or polypoid type with suspected deep invasion or invasion extending outside the bronchial wall based on the bronchoscopic finding and thin-slice computed tomographic scan, we perform parenchymal-sparing limited bronchoplasty, if it is thought that the tumor can be removed completely by this procedure. (4) Even in advanced cancer, we perform radical operation if the patient is thought to have sufficient cardiopulmonary reserve to undergo this operation.
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Footnotes
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Address reprint requests to Dr Watanabe, Department of Surgery, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa 920, Japan.
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References
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Abstract
Introduction
